A brain-enriched lncRNA shields cancer cells from immune-mediated killing for metastatic colonization in the brain

Significance Brain metastasis with current limited treatment options is a common complication in advanced cancer patients, and breast-to-brain metastasis (B2BM) is one of the major types. In this work, we report that brain metastasis oncogenic long noncoding RNA (BMOR) is a key brain-enriched long noncoding RNA for the development of B2BM. We demonstrate that BMOR allows B2BM cells to colonize the brain tissue by evading immune-mediated killing in the brain microenvironment. At the molecular level, BMOR binds and inactivates IRF3 in B2BM cells. Finally, BMOR silencer can effectively suppress the development of brain metastasis in vivo. Therefore, our findings reveal a way in which cancer cells evade immune-mediated killing in the brain microenvironment for brain metastasis development and establish therapeutic targets with potential targeted strategies against B2BM.